Corso di disegno 2 by Gaspare De Fiore

By Gaspare De Fiore

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These studies will be complemented by examinations of alterations in control of the vasoconstrictor and vasodilator pathways between active and placebo phases of oral contraceptives. The applicant will evaluate peripheral contributions by these steroids in vasomotor function by testing whether vasoconstrictor responses to controlled application of norepinephrine or vasodilator responses to direct application of acetylcholine are dependent on the phase of the menstrual cycle. This question will be further addressed by finding if the level of skin blood flow in areas free of autonomic influences (via cutaneous nerve block) and in areas with intact innervation vary among phases of the menstrual cycle or between phases of oral contraceptive use.

This proposal investigates the function of three important coactivators, Steroid Receptor Coactivator-1 (SRC-1), SRC-3 and CREB Binding Protein (CBP), in estrogen receptor (ER) action in brain and the regulation of behavior. Aim 1 will determine if SRC-3, which has recently been shown to be essential for female reproductive physiology, is expressed in steroid receptorcontaining neurons in brain regions known to regulate reproductive behavior. In support, we have found that SRC-1 and CBP are expressed in steroid sensitive cells in behaviorally-relevant brain areas.

We will conduct integrated pharmacokinetic and efficacy studies in castrated and intact male rats to determine the in vivo pharmacologic activity, bioavailability, and pharmacokinetics of these drugs. The overall goal of these studies is to develop structure-activity relationships based on the physicochemical and pharmacokinetic properties of these drugs. , Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Neurosteroids, steroids synthesized in the brain, have been implicated in functions ranging from stress, depression, anxiety, to cognition.

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